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Compounds with sulfhydryl substituents and azole compounds exhibit potent anti-tyrosinase potency. 2-Thiobenzothiazole (2-TBT), a hybrid structure of sulfhydryl and azole, exists in two tautomeric forms, with the thione form being predominant according to several studies. 2-TBT derivatives were synthesized as potential tyrosinase inhibitors as the thione tautomeric form has the same N-CS moiety as phenylthiourea (PTU), which is suitable for chelation with the copper ions present in the tyrosinase active site. Eight of the ten 2-TBT derivatives inhibited the monophenolase and diphenolase activities of mushroom tyrosinase, with IC 50 values of 0.02-0.83 μM. Kinetic studies and molecular dynamics simulations were performed to determine their mode of action and confirm that the 2-TBT derivatives bind to the tyrosinase active site with high stability. Derivatives 3, 4, 8, and 10 strongly inhibited melanogenesis in B16F10 cells in a pattern similar to the results of cellular tyrosinase inhibition, thereby suggesting that their ability to inhibit melanogenesis was due to their tyrosinase inhibitory activity. In a depigmentation experiment using zebrafish embryos, all 2-TBT derivatives showed better potency than kojic acid, even at 400 to 2000 times lower concentration, and 1 and 10 reduced zebrafish larva pigmentation more strongly than PTU even at 20 times lower concentration. Experiments investigating the changes in tyrosinase inhibitory activity of 2-TBT derivatives in the presence and absence of CuSO 4 and their copper chelating ability supported that these derivatives exert their anti-melanogenic effect by chelating the copper ions of tyrosinase. These results suggest that 2-TBT derivatives are promising candidates for the treatment of hyperpigmentation-related disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

As the β-phenyl-α,β-unsaturated carbonyl (PUSC) structure was previously identified to play a key role in tyrosinase inhibition, 14 analogs with a PUSC structure built on a thiazol-4(5H)-one scaffold were synthesized using Knoevenagel condensation to serve as potential tyrosinase inhibitors. Through mushroom tyrosinase inhibition experiments, two analogs 9 and 11 were identified as potent tyrosinase inhibitors, with 11 exhibiting an IC 50 value of 0.4 ± 0.01 μM, which indicates its 26-fold greater potency than kojic acid. Kinetic studies using Lineweaver-Burk plots revealed that 9 and 11 are competitive and mixed-type inhibitors, respectively; these kinetic results were supported by docking simulations. According to the B16F10 cell-based experiments, 9 and 11 inhibited melanogenesis more effectively than kojic acid due to their potent cellular tyrosinase inhibitory activity. In addition, analogs 9 and 11 exhibited moderate-to-strong antioxidant capacity, scavenging ABTS + , DPPH, and ROS radicals. In particular, analog 12 with a catechol moiety exhibited very strong ROS-scavenging activity, similar to Trolox. These results suggest that analogs 9 and 11, which exhibit potent tyrosinase inhibitory activity in mushroom and mammalian cells and anti-melanogenic effects in B16F10 cells, are promising antibrowning agents for crops and skin lightening agents for hyperpigmentation-related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: The aim is to examine trends in procedural indication, arterial beds treated, and device usage in peripheral arterial interventions (PVIs)., Background: There is little data on indication, vascular beds treated and devices utilized for peripheral arterial interventions., Methods: We used data from 43 hospitals participating in the BMC2 VIC registry. PVIs were separated by year and divided by arterial segment. Lower extremity PVIs were subclassified as having been performed for claudication or critical limb ischemia (CLI). Yearly device usage was also included. A repeated measure ANOVA was used to determine trends., Results: 44,650 PVIs were performed from 2006 to 2013. Renal interventions decreased from 18% of interventions in 2006 to 5.6% in 2013 (P < 0.001) and femoral-popliteal increased from 54.9% in 2006 to 64.5% in 2013 (P < 0.001). No significant trend was seen for aorta-iliac or below-the-knee interventions. 58.6% of PVIs were performed for claudication in 2006 and this decreased to 44.6% in 2013 (P = 0.025). Indications for CLI were 24.1% in 2006 and 47.5% in 2013 (P < 0.001). There were significant increases in the use of balloon angioplasty (P = 0.029) and cutting/scoring balloons (P < 0.001) while cryoballoon usage decreased (P < 0.001). No significant changes were found with stenting, atherectomy, and laser., Conclusions: There is a significant increase in patients presenting with CLI. Renal artery intervention rates are decreasing while femoral-popliteal interventions are increasing. Additionally, balloon angioplasty and cutting/scoring balloon usage is increasing. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)